Surgical implantation of biological materials is a frequently employed technique and finds application in many areas of medicine. The material may originate from the recipient himself (autologous tissue), from the same species as the recipient (homologous tissue), or heterologous tissue). Examples of such biological materials are cardiac valves, pericardium, sinews, tendons, ligaments, dura mater, bones, skin, collagen, arteries, veins, etc. Various methods, which reduce the implant these materials as a replacement for or repair of certain defects in man since in the absence of appropriate pretreatments, the biological materials can lead to rejection reactions in man.
Methods of reducing antigenicity mainly have the intent of fixing, that is, denaturing the tissue. For this purpose, these materials are treated with aldehydes, such as glutaraldehyde, formaldehyde and glyoxal. Glutaraldehyde and formaldehyde are the reagents used most, since they are known to have a sterilizing effect. Moreover, they are known to have a good denaturing effect, that is, they reduce the antigenicity of the material to such an extent, that rejection reactions no longer occur after implantation. However, the aldehyde residues present in the tissue must be removed as completely possible, since the aldehydes can cause severe irritations, such as inflammatory reactions or other harmful effects, after implantation. For this purpose, the biological materials are treated before implantation with sterile solutions, such as doubly distilled (oil) water, or with isotonic salt solutions, in order to remove the residues of unbound aldehydes.
It is also already known to remove the aldehydes by the addition of aminodicarboxylic acids. The aldehyde removal reaction is carried out in a medium having a pH greater than 7. These methods, moreover, are based on the principle of a Schiff's base reaction between free, diffusible aldehydes in the tissue and the NH.sub.2 groups of the added substance. As the pH increases, Schiff's base reaction. For this reason, care is always taken to ensure that the reaction is conducted in an appropriately neutral to alkaline medium. Aside from aminocarboxylic acids, primary, secondary and tertiary amines, as well as mixtures of these amines are suitable for these reactions.
Such methods, however, still leave significant amounts of aldehyde in the tissue. As a result, the remaining aldehydes, can cause an inflammatory reaction.
It is therefore an object of the invention to provide a method of removing aldehydes from biological materials to the extent that they no longer cause irritation in adjacent tissue.